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pmid:35462848
Identification of a Four-Gene Metabolic Signature to Evaluate the Prognosis of Colon Adenocarcinoma Patients.
Yang Zheng · Rilige Wu · Ximo Wang · Chengliang Yin
Frontiers in public health · 2022 doi:10.3389/fpubh.2022.860381
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Experiment
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Complete file
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Metabolic reprogramming is emerging as a novel cancer hallmark that may serve as the basis for more effective prognosis strategies.\nMethods: The mRNA expression profiles and relevant clinical information of COAD patients were downloaded from public resources. The least absolute shrinkage and selection operator (LASSO) Cox regression model was exploited to establish a prognostic model, which was performed to gain risk scores for multiple genes in The Cancer Genome Atlas (TCGA) COAD patients and validated in GSE39582 cohort. A forest plot and nomogram were constructed to visualize the data. The clinical nomogram was calibrated using a calibration curve coupled with decision curve analysis (DCA). The association between the model genes' expression and six types of infiltrating immunocytes was evaluated. Apoptosis, cell cycle assays and cell transfection experiments were performed.\nResults: Univariate Cox regression analysis results indicated that ten differentially expressed genes (DEGs) were related with disease-free survival (DFS) (P-value< 0.01). A four-gene signature was developed to classify patients into high- and low-risk groups. And patients with high-risk exhibited obviously lower DFS in the training and validation cohorts (P < 0.05). The risk score was an independent parameter of the multivariate Cox regression analyses of DFS in the training cohort (HR > 1, P-value< 0.001). The same findings for overall survival (OS) were obtained GO enrichment analysis revealed several metabolic pathways with significant DEGs enrichment, G1/S transition of mitotic cell cycle, CD8+ T-cells and B-cells may be significantly associated with COAD in DFS and OS. These findings demonstrate that si-FUT1 inhibited cell migration and facilitated apoptosis in COAD.\nConclusion: This research reveals that a novel metabolic gene signature could be used to evaluate the prognosis of COAD, and targeting metabolic pathways may serve as a therapeutic alternative.", "claims": [{"id": "claim-method", "statement": "To reduce the number of genes, we used the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to screen genes for DFS and OS, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35462848", "locator": "sections[4] \"Building and Verification of a Prognostic Model of Metabolic-Related Genes\" paragraph 3", "quote": "To reduce the number of genes, we used the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to screen genes for DFS and OS, respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35462848", "locator": "sections[22] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A four-gene metabolic prognostic signature classified COAD patients into high- and low-risk groups and was an independent prognostic parameter for disease-free survival in the training cohort.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35462848", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A four-gene signature was developed to classify patients into high- and low-risk groups."}, {"asset": "source:pmid:35462848", "locator": "sections[16] \"The Prognostic Model as an Independent Clinical Parameter\" paragraph 2", "quote": "Multivariate Cox regression analysis revealed that this prognostic model was an independent prognostic parameter of DFS (Figure 3A)."}, {"asset": "source:pmid:35462848", "locator": "sections[15] \"Independent Prognostic Role of the Prognostic Model\" paragraph 2", "quote": "The AUCs of 1-, 3-, and 5-year predicted by the risk score were 0.779, 0.798, and 0.845, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A four-gene metabolic prognostic signature classified COAD patients into high- and low-risk groups and was an independent prognostic parameter for disease-free survival in the training cohort.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35462848"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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